Body fluid homeostasis largely depends upon precise regulation of both the intake and excretion of water and sodium, the major constituents of the extracellular fluid. The physiological consequences of water and sodium deficiency have been studied extensively and are well known. Most prominent are the changes in the concentration and distribution of body fluids and the increased activity of various neuroendocrine systems. Experimental procedures involving different diets, treatments, and surgical techniques have been developed to independently manipulate each of these variables in rats both in acute and chronic conditions, while separate procedures are available to assay the stimulus conditions. These procedures will be combined with behavioral tests in order to isolate the specific stimuli which mediate the appetites for water and sodium and to determine their interaction. More specifically, the proposed research examines the relationship between fluid intake and blood volume regulation, with particular emphasis on the mechanisms which stimulate thirst and sodium appetite during hypovolemia. The contribution of the renin-angiotensin- aldosterone system will be examined in several experiments using radioimmunoassay procedures for measuring circulating hormone levels. Other work will study relevant neural factors, especially the role of biogenic amines in the central neural control of fluid balance. This latter work will involve specific destruction of brain catecholamine- containing neurons and chemical assays of residual neuron function. Various metabolic factors which might influence sodium appetite, such as uremia and the sodium exchanges in bone, also will be examined in a series of studies designed to elucidate their effects on sodium balance. In short, these experiments will attempt to identify the major physiological and motivational variables involved in the regulation of body fluid balance, and the specific central neural mechanisms which might mediate these phenomena.